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Biomedical subjects

C D Haas

Publications and source records attributed to C D Haas.

At least 19 recordsLinked to original sources
PubMed1987

Cisplatin and fluorouracil as neoadjuvant therapy in head and neck cancer. A preliminary report.

A randomized, prospective trial utilizing cisplatin and fluorouracil as neoadjuvant chemotherapy in the treatment of advanced squamous cell carcinomas of the upper aerodigestive tract was initiated in January 1983. Sixty patients were stratified by site (oral cavity, 19; larynx, 14; hypopharynx, 14; oropharynx, 11; nasopharynx, one; and paranasal sinuses, one) and by stage (III, 19; IV, 41), and then randomized to receive either standard treatment (defined as preoperative irradiation followed by radical excision or irradiation alone) or adjuvant chemotherapy followed by standard treatment. An additional three patients were entered into the study, but withdrew. Chemotherapy consisted of three cycles for those patients in whom an objective tumor response was observed; nonresponders received standard treatment. Response to chemotherapy was complete in five and partial (greater than 50%) in 18 patients, for an overall response rate of 85%. The follow-up for surviving patients was a minimum of 24 months and a maximum of 44 months. Survival was compared for patients in both treatment groups according to the method of Lee and Desu. Despite excellent tumor response, actuarial survival was 70% in the standard treatment group as opposed to 56% in the experimental group. It was therefore evident that the high response rates reported in previous pilot studies do not necessarily result in improved survival in these cancers.

Carcinoma, Squamous Cell↗
PubMed1987

Phase I study of echinomycin.

Echinomycin was administered to patients with advanced carcinoma in escalating doses ranging from 60 to 1500 micrograms/m2 given weekly by 15-minute iv infusions for four doses, with a subsequent 2-week rest period. Dose-limiting nausea, vomiting, and anorexia associated with varying degrees of renal and hepatic dysfunction proved dose-limiting at the 1500-micrograms/m2 level. Thrombocytopenia was noted in 15% of patients receiving greater than or equal to 700 micrograms/m2 and was severe in 11% without an evident dose-response relationship. Leukopenia was rare and mild when encountered. Allergic reactions were observed. Phase II trials are feasible using a dose schedule of 1200 micrograms/m2/week X 4 weeks.

Carcinoma↗
PubMed1986

Phase I evaluation and clinical pharmacology of tricyclic nucleoside 5'-phosphate using a weekly intravenous regimen.

Tricyclic nucleoside phosphate (TCN-P) was selected for clinical trials because of its unusual chemical structure and activity against L1210 murine leukemia and MX-1 mammary xenograft. Inhibiting DNA synthesis, TCN-P was more toxic during S-phase of cell cycle. A phase I study was conducted in 24 patients with advanced solid cancers. The drug was given as a slow i.v. injection over 5 min on Days 1, 8, 15, and 22 of a 42-day cycle with a 2-week rest. Five dose levels ranging from 12 to 96 mg/m2 were studied with 3 to 12 patients treated at each level; a total of 106 doses was administered. The major hematological toxicity was thrombocytopenia, with a median nadir occurring at Day 34 of the cycle and first appearing at doses greater than 24 mg/m2. Anemia was seen at each dose level occurring between Days 8 and 34. Non-myelosuppressive toxic effects included stomatitis, anorexia, transient fever, nausea and vomiting, and dose-limiting hyperglycemia and diarrhea. The highest tolerated dose was 48 mg/m2. Plasma, pleural fluid, urine, and tissue samples were analyzed for TCN-P and tricyclic nucleoside (TCN) in selected patients by high-performance liquid chromatography. Plasma decay curves revealed extended retention of both TCN and TCN-P. Autopsy specimens obtained 61 days after therapy showed the highest residues of TCN-P in liver metastases and of TCN in gall bladder, bile, and pancreas. No drug was detected in urine samples of two patients. Prolonged retention and erratic plasma levels of the drug are probably due to extensive enterohepatic circulation, as well as repeated interconversion between TCN-P and TCN within cells. This weekly schedule produced unexpected clinical toxicity and should not be pursued.

Acenaphthenes↗
PubMed1985

Phase I evaluation of chlorozotocin (NSC-178248): weekly schedule.

A phase I trial of chlorozotocin was completed for a weekly times four dose schedule repeated every 8 weeks. Thrombocytopenia was the acute dose limiting toxicity. Nausea and vomiting were moderate to severe and dose related. Two cases of possible drug related irreversible nephrotoxicity were seen. Transient elevations of serum creatinine and mild proteinuria were noted. Also, transient elevations in SGOT were observed. One patient with a carcinoid tumor had a 60% reduction in his 5HIAA level after one course of therapy. The recommended dose for phase II clinical studies of chlorozotocin is 40 mg/m2 IV weekly for four weeks, repeated every 8 weeks.

Adult↗
PubMed1985

Dibromodulcitol (DBD), DTIC, and actinomycin-D in disseminated malignant melanoma. A phase I-II clinical trial.

Thirty-seven fully assessable patients with metastatic malignant melanoma were administered DTIC, actinomycin-D, and dibromodulcitol (DBD) on a q 3- to 4-week schedule. Doses of actinomycin-D and DTIC were 1.25 mg/m2 and 750 mg/m2, respectively, on day 1. DBD was progressively escalated in five dose levels in succeeding patients from an initial 90 mg/m2 daily, days 3-7, to a dose-limiting 230 mg/m2. Two complete and nine partial responses were observed for an overall response rate of 30%. Median duration of response was 18 weeks. Major toxicities observed were hematologic and gastrointestinal. Median survival of all patients was 30 weeks and did not differ significantly from our earlier trials of DTIC and actinomycin-D +/- chlorozotocin. Although the observed objective response rate was higher than our previous efforts in this disease, the addition of DBD failed to significantly impact on the survival of the entire treatment group. Further investigation of this chemotherapy combination does not appear warranted.

Adult↗
PubMed1985

Phase II evaluation of aclacinomycin-A in patients with adenocarcinoma and large cell carcinoma of the lung.

Aclacinomycin-A (ACLA-A), the new anthracycline antibiotic that produces substantially less cardiotoxicity relative to doxorubicin, was evaluated in a phase II trial for advanced large cell and adenocarcinoma of the lung patients. Twenty-three patients with measurable disease were entered into the trial and received ACLA-A in doses of a weekly infusion of 65 mg/m2 and 85 mg/m2. Eighteen patients were evaluable for response and toxicity. Two patients were evaluable for toxicity only, one died before completion of a full course of therapy, and two did not receive the drug. There were no complete or partial remissions in this study. Three patients had disease stabilization for a median of 10 weeks (range 6-17). Toxicity was mainly hematologic. Nausea and vomiting were moderate. ACLA-A, in the dose schedules used, appears to have no activity in large cell and adenocarcinoma of the lung.

Aclarubicin↗
PubMed1984

Chlorozotocin: results in colorectal carcinoma treated with high and low doses. A Southwest Oncology Group study.

Clorozotocin was evaluated in patients with advanced colorectal cancer at 225 mg/m2 every six weeks in 14 patients with no prior treatment, at 200 mg/m2 in 43 patients with normal tolerance of prior chemotherapy, and at 100 mg/m2 in 38 patients with extensive or poorly tolerated prior therapy. Median survival for the respective groups was 192, 107 and 79 days; these differences are best explained as a function of performance status. Partial response was reported for one patient, 15 had disease stabilization and two had improvement short of partial remission. Myelotoxicity was acceptable at all doses, with thrombocytopenia being dose limiting at 225 mg/m2. Four patients developed azotemia during or after chlorozotocin treatment. Chlorozotocin has minimal activity against colorectal carcinomas and no dose-response relationship is evident.

Adenocarcinoma↗
PubMed1984

Nafazatrom: in-vitro assessment of radiation and drug activity against animal and human cell lines.

The B-16 melanoma animal cell line and HEC-1A human endometrial cell line treated with Nafazatrom (NFZ) (5 mu/ml) and varying doses of ionizing radiation show a dose response curve of increased colony inhibition with increasing radiation dose. The B-16 line consistently demonstrated enhanced colony inhibition when NFZ was added prior to radiation. This colony inhibition by NFZ was not seen in the HEC-1A cell line. No adverse effect, i.e., increased tumor colony growth, was evident when NFZ and radiation were combined. This study suggests that ionizing radiation can be combined with NFZ without adverse effect on the cell killing effects of either modality.

Adenocarcinoma↗
PubMed1984

Nafazatrom: clonogenic in-vitro assessment of activity against human malignancies.

Nafazatrom was tested against a variety of human malignancies with the human tumor stem cell assay at one or more of the following concentrations: 1, 10, 25, and 100 micrograms/ml X 1 h or 0.05, 0.5, or 5 micrograms/ml by continuous exposure. Major (greater than or equal to 70%) inhibition was noted in 7/52 adenocarcinomas, in 0/9 squamous carcinomas, and 1/17 other malignancies. Intermediate levels of inhibition (50 to 69%) were noted in 7/52, 4/9, and 6/17 of these respective subtypes. No clear trend toward superiority of any dose-schedule was noted. Since nafazatrom has proven non-toxic in our nearly completed Phase I study, and since this study suggests activity against several human cancers, Phase II level testing is warranted.

Adenocarcinoma↗
PubMed1984

Phase I and pharmacologic evaluation of nafazatrom in patients with cancer.

Nafazatrom was evaluated in escalating daily oral doses ranging from 0.25 to 8.0 g/m2 without producing significant toxicities. Malabsorption proved dose limiting at 8.0 g/m2 as a single daily dose, but splitting the same total dose into two or four doses circumvented this problem. Doses of 2.0 g/m2 at 6-h intervals or 4.0 g/m2 every 12 h are reasonable for Phase II and adjuvant trials. Pharmacologic evaluation of nafazatrom confirmed malabsorption at the highest single daily dose level tested and suggests that absorption was impaired in patients with extensive liver metastases.

Adult↗
PubMed1984

Phase I evaluation of AT-125 single dose every three weeks.

A Phase I trial of AT-125 was completed for the bolus dose every three week schedule. Dose limiting toxicity was primarily central nervous system (CNS) in the form of ataxia, confusion, hallucinations and dysarthria. Although this was most severe at doses of 150 mg/m2, lesser symptoms were reported at all dose levels. Nausea and vomiting were moderate to severe at higher doses. Myelosuppression did not occur. This schedule is not recommended for Phase II studies until methods are developed to reduce drug-related CNS toxicity.

Adult↗
PubMed1984

Phase II clinical evaluation of AZQ in adenocarcinoma of the lung.

Twenty patients with advanced measurable adenocarcinoma of the lung were treated with AZQ 20 mg/m2 weekly for 4 weeks, followed by a 2-week rest. No complete or partial responses were observed. Stabilization was observed in seven individuals, lasting 6-32+ weeks, with a median of 6 weeks. Toxicity was limited to reversible myelosuppression. We conclude that AZQ administered at this dose and schedule has no significant activity against advanced adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1983

Phase I trial of Indicine-N-Oxide on two dose schedules.

Indicine-N-Oxide is the water soluble N-oxide of the pyrolizidine alkaloid indicine recently evaluated in Phase I trials. Initially in a weekly times four schedule, twenty-nine patients were treated with a dose range of 1.0 to 7.5 g/m2 per week. Fifteen of 40 of the courses of four doses were interrupted by myelosuppression which prohibited completion of the course. Therefore, an intermittent schedule was evaluated utilizing single doses repeated every 3-4 weeks. Twenty-six patients were treated at doses of 5 to 10 g/m2. Myelosuppression is the dose limiting toxicity of both schedules with thrombocytopenia being more severe than leukopenia. Myelosuppression is predictable and reversible on the intermittent schedule. It is more severe in patients with heavy prior treatment. Partial responses were seen in four patients, one with a mucoepidermoid carcinoma of the salivary gland and three with adenocarcinoma of the colon. Phase II studies are planned at a starting dose of 7.5 g/m2 every 3-4 weeks in patients with no prior treatment and 5 g/m2 in patients with prior treatment.

Adult↗
PubMed1983

Phase II evaluation of galactitol in head and neck cancer: a Southwest Oncology Group Study.

A phase II evaluation of DAG in head and neck cancer patients produced one partial response and one patient with prolonged stable disease from nine fully evaluable patients with squamous carcinomas. One partial response was produced in a patient with anaplastic thyroid carcinoma. No drug deaths or life-threatening toxicity were reported. Further evaluation of DAG in thyroid tumors is warranted.

Adult↗
PubMed1983

Vindesine in head and neck cancer. A Southwest Oncology Group Phase II pilot study.

Vindesine was tested in 23 fully evaluable patients with advanced carcinomas of the head and neck. All had received previous chemotherapy. No complete or partial responses resulted after one or more courses of 1.5 mg/m2 i.v. bolus daily X 2 days. Leukopenia was noted in 46% and peripheral neuropathy was reported in 29%. This dose-schedule of vindesine is inactive in previously treated patients with squamous carcinomas of the head and neck.

Antineoplastic Agents↗
PubMed1983

Phase I evaluation and pharmacokinetics of aziridinylbenzoquinone using a weekly intravenous schedule.

Quinone derivatives have shown intensive antitumor activity in a broad variety of neoplasias. Aziridinylbenzoquinone is designed to have adequate lipid solubility to attain useful drug concentrations in the central nervous system. A Phase I study of aziridinylbenzoquinone was conducted in 32 patients with advanced solid cancers. The drug was given as a slow i.v. injection on Days 1, 8, 15, and 22 of a 42-day cycle with a 2-week rest. Five dose levels ranging from 5 to 20 mg/sq m were studied, with 3 to 10 patients treated at each level; a total of 156 doses were administered. The major toxicity was myelosuppression with the median nadir in platelet and white blood cells occurring at Days 15 to 27 of the cycle, and first appearing at doses greater than 10 mg/sq m. Anemia was first seen at the 10-mg/sq m dose level, occurring between Days 22 and 40. Nonmyelosuppressive toxic effects included nausea and vomiting, anorexia, diarrhea, stomatitis, slight alopecia, and transient fever. The highest tolerated dose was 20 mg/sq m, the recommended dose for Phase II studies. Plasma and urine pharmacokinetics were studied in 17 patients by a high-pressure liquid chromatography method. Plasma decay curves could be fitted to a two-compartment open-system model with an overall average alpha and beta half-life values of 10.5 +/- 6.28 min and 16.90 +/- 8.63 (S.D.) hr. Aziridinylbenzoquinone levels were determined in urine samples of 12 patients, but less than 0.1% of the dose was excreted in the 0- to 4-hr sample of two patients, and none was detected in the urine of 10 patients.

Antineoplastic Agents↗
PubMed1983

Phase II evaluation of 1-(2-chloroethyl)-3-(2,6-dioxo-(piperidyl)-1 nitrosourea (PCNU)(NSC-95466) in patients with advanced carcinoma of the lung.

Sixty-one assessable patients with advanced small cell and non-small cell carcinoma of the lung were given PCNU on an intermittent every 6-week schedule. Starting doses ranged from 75 mg/m2 for poor-risk patients to 100 mg/m2 for good-risk patients, depending on the bone marrow, liver, and renal status. Six partial responses (two small cell carcinoma, two adenocarcinoma, two large cell carcinoma) of short duration were documented. The major toxic effects were thrombocytopenia (35%) and leukopenia (16%). PCNU does not appear to have sufficient antitumor activity to warrant further investigation in advanced lung cancer.

Aged↗